Borrelia burgdorferi rapidly disrupts gastrointestinal immune barrier function, inducing a 'leaky gut' syndrome characterized by increased gut permeability, systemic endotoxemia, and suppressed humoral immunity to the microbiota, with similar blood changes observed in patients with acute Lyme disease that correlated with disease symptoms and largely resolved after antibiotic treatment.
Key Findings
Results
Borrelia burgdorferi infection rapidly induces a 'leaky gut' syndrome in mice characterized by increased gut permeability and systemic endotoxemia.
Infection caused increased gut permeability as measured by established permeability assays in mouse models
Systemic endotoxemia was documented following Bb infection
Elevated LPS binding protein (LBP) and intestinal fatty acid binding protein (I-FABP) were observed in infected mice
Altered blood leukocyte profiles accompanied these gut barrier disruptions
These changes occurred rapidly following infection
Results
Patients with acute Lyme disease showed blood changes similar to those seen in Bb-infected mice, including markers of gut permeability and endotoxemia.
Human patients with acute Lyme disease demonstrated elevated markers consistent with leaky gut syndrome
Blood changes in patients correlated with disease symptoms
Blood changes also correlated with liver function measurements
These changes largely resolved after antibiotic treatment
The human findings mirrored the mechanistic findings from the mouse model
Results
Bb infection suppressed humoral immunity to the gut microbiota, resulting in reduced IgA coating of fecal microbes and decreased antimicrobial serum IgG.
IgA coating of fecal microbes was reduced following Bb infection
Antimicrobial serum IgG levels were decreased despite increased gut permeability
This suppression of humoral immunity occurred despite the heightened antigen exposure implied by a leaky gut
The reduction in microbiota-directed antibody responses was identified as a mechanistic feature of Bb-induced disease
These immune defects were identified as potentially driving disease pathology
Results
Bb infection triggered mild early inflammation in the small intestine that preceded later shifts in gut bacterial composition and short-chain fatty acid production.
Early mild inflammation was observed specifically in the small intestine
Shifts in gut bacterial (microbiome) composition were observed at later time points
Decreased short-chain fatty acid (SCFA) production was also observed at later time points
The sequence of events suggests that immune barrier dysfunction and impaired humoral immunity precede and potentially drive microbiota compositional changes
This temporal ordering supports a mechanistic role for barrier dysfunction in downstream gut dysbiosis
Discussion
Mucosal barrier dysfunction and impaired antimicrobial humoral immunity are identified as potential mechanistic drivers of Borrelia burgdorferi-induced disease.
The study proposes a mechanistic pathway linking Bb infection to gut barrier disruption and immune suppression
Impaired microbiota-antibody interactions (both IgA and IgG) are highlighted as novel features of Bb infection
These findings may help explain the myriad symptoms of unknown causes seen in Lyme disease patients
The correlation of gut permeability markers with clinical symptoms in human patients supports translational relevance
The authors frame these defects as 'potential drivers of Bb-induced disease'
What This Means
This research suggests that the bacterium that causes Lyme disease, Borrelia burgdorferi, does more damage than previously recognized by disrupting the protective barrier of the gut. In mouse experiments, infection quickly led to what is commonly called 'leaky gut' — a condition where the intestinal lining becomes more permeable, allowing bacterial products like LPS (a component of gut bacteria) to leak into the bloodstream. This leakage triggered systemic inflammation and altered immune cell profiles in the blood. Importantly, people diagnosed with acute Lyme disease showed the same blood markers of gut leakage, and these markers correlated with how sick patients felt and with liver function abnormalities. After antibiotic treatment, these markers largely returned to normal in patients.
The study also uncovered an unexpected immune suppression specifically targeting the gut. Normally, the immune system produces antibodies — particularly IgA in the gut and IgG in the blood — that help control the billions of bacteria living in the intestines and keep them from causing harm. Bb infection reduced both of these antibody responses to gut microbes, even while the gut was leaking more bacterial products into the body. This means the immune system was simultaneously overwhelmed with more microbial exposure and less equipped to handle it. These antibody defects appeared before later-observed changes in the actual composition of gut bacteria and in the production of beneficial short-chain fatty acids.
This research suggests that Lyme disease is not just a problem of the joints, nervous system, or heart — it also significantly disrupts the gut immune barrier and the body's ability to manage its own microbiome. These gut disruptions may contribute to the wide variety of symptoms that Lyme disease patients experience, including some that have been difficult to explain. The finding that antibiotic treatment helps resolve these gut-related blood markers in human patients is encouraging, but the identification of these gut immune defects opens new questions about whether they contribute to prolonged symptoms in some patients and whether gut health should be considered in Lyme disease management.
Sachan S, Tran G, Olsen K, Kulaga H, Day A, Savage H, et al.. (2026). Borrelia burgdorferi disrupts gut barrier functions and microbiota-antibody interactions.. The Journal of experimental medicine. https://doi.org/10.1084/jem.20252380